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Updated: Sep 29, 2025

Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder
Published on: January 9, 2015
N-acetyl cysteine (NAC) augmentation in the treatment of obsessive-compulsive disorder: A phase III, 20-week,
Jerome Sarris1, Gerard Byrne2, David Castle3
1NICM Health Research Institute, Western Sydney University, Westmead, NSW, Australia; Florey Institute for Neuroscience and Mental Health, Kenneth Myer Building, Royal Parade, Parkville, Melbourne, Victoria, Australia; Professorial Unit, The Melbourne Clinic, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia.
Objective:
Preliminary evidence has suggested that adjunctive N-acetylcysteine (NAC), an antioxidant precursor to glutathione, may reduce symptoms of obsessive-compulsive disorder (OCD). We conducted a 20-week, multi-site, randomized controlled trial to investigate the safety and efficacy of the adjunctive use of NAC in OCD.
Methods:
The study was a phase III, 20-week, double-blind, randomized controlled trial across multiple sites in Australia investigating 2 g to 4 g per day of NAC (titrated according to response) in 98 participants with DSM-5 diagnosed OCD. Data were analysed using linear mixed effects models for the 89 participants who attended at least one follow-up visit.
Results:
A modified intention-to-treat analysis of the primary outcome found no evidence that NAC reduced symptoms of OCD measured on the Yale-Brown Obsessive-Compulsive Scale, relative to placebo (mean difference at week 20 = 0.53, 95% compatibility interval = -2.18, 3.23; p = 0.70; favouring placebo). There was also no evidence that NAC, compared to placebo, improved outcomes on the secondary measures including anxiety, depression, quality of life, functioning, or clinician/participant impression. NAC was well-tolerated with only mild gastrointestinal adverse events associated with the treatment.
Conclusion:
We found no evidence supporting the efficacy of the adjunctive use of NAC in OCD.
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